Research Progress of the UPR Mechanism and its Effect on Improving Foreign Protein Expression

2020 ◽  
Vol 27 (9) ◽  
pp. 831-840
Author(s):  
Bao-Chen Wang ◽  
Si-Tong Zhang ◽  
Guang Chen

: The unfolded protein response (UPR) is a protective mechanism against endoplasmic reticulum (ER) stress that induces a series of signal transduction pathways to eliminate misfolded proteins. The UPR mechanism is highly conserved in fungi, higher organisms, plants and mammals. The UPR pathway is activated to stabilize ER functions when there are too many unfolded proteins or misfolded proteins in the ER. However, stress continues when ER proteins are stimulated by toxic substances that affect the balance of the UPR pathway, which causes changes in the structure and function of the ER and other organelles. These ultimately disrupt homeostasis in the body and cause pathological reactions that can be fatal. The UPR mechanism has clear effects on stabilizing the protein-folding environment. Dysfunction or disruption of the UPR mechanism is associated with numerous disorders, including neurodegenerative diseases, loss of control of protein secretion, cerebral ischemia and epilepsy, neuropsychiatric diseases, eye diseases, skin diseases, metabolic and inflammatory diseases, atherosclerosis, and heart disease. Thus, characterization of UPR function and its dysfunction has significant importance and has broad application prospects, which make research into the UPR a research hotspot.

1912 ◽  
Vol 16 (1) ◽  
pp. 78-102 ◽  
Author(s):  
Augustus B. Wadsworth

From the results of this study of the action of immune sera on pneumococcus infection it is evident that immune sera vary greatly in their curative value. Immune sera possess protective action, but protective action is not necessarily indicative of curative action. Treatment with the serum of normal rabbits may prolong the course of pneumococcus infection in the rabbit. This action, however, is slight and not always manifest. Sera from animals immunized with dead pneumococcus cells which had been washed free from their products, failed to exert materially greater curative action than normal sera. Sera from animals immunized with culture filtrates free from pneumococcus cells possessed, in some instances, a slight curative value, but often this curative action was not apparent. In animals actively immunized, however, the presence of an immunity to culture filtrates was readily demonstrated. In the immunity produced by injections of dead culture material the strength was not sufficiently exalted for the sera to possess a practical curative value. It was only after immunization with virulent living cultures that the blood serum acquired marked curative action. After pneumococcus infection in the rabbit had become established, treatment with this serum induced crisis and cured the animals. From the results of the study of the mechanism of recovery it is evident that, despite the fact that virulent pneumococci are singularly insusceptible to the action of immune sera in the test-tube, pneumococcus infection nevertheless conforms to the general law of infection. Diphtheria and tetanus organisms give rise to powerful toxins, but the parasitism of these organisms is slight and their development is localized. Diseases produced by these organisms are toxemias and neutralization of their toxins by antitoxin puts an end to the disease. The pneumococcus gives rise to toxic substances which are less active or are active only in the body tissues, but the parasitism of this organism is marked and its development is rarely localized. Nevertheless, the manifestations of the disease arise from the action of the bacterial poisons on the tissues. The neutralization of the pneumococcus poisons by immune serum puts an end to the symptoms of the disease, but the pneumococci survive as harmless parasites until destroyed by lysis or phagocytosis. The neutralization of the pneumococcus poison may take place suddenly and completely as in crises; or, it may be incomplete with exacerbations of infection, as in lysis. Crisis, as it occurs in the lobar pneumonia of man and in the bacteriemia of the rabbit, is simply one phase of recovery, and recovery does not differ fundamentally, whether it is sudden and complete as in crisis, or incomplete and prolonged as in lysis, or whether the pneumococci are destroyed by lysis extracellularly as in the rabbit, or intracellularly as in the phagocytosis of the dog and man. Since the recovery of animals from pneumococcus infection differs in no essential from that of man, since the unaided protective mechanism of man as compared with that of susceptible animals is exceptionally efficient, and since it is possible by treatment with sera from animals highly immunized with living cultures of virulent pneumococci to cure pneumococcus infection in the most susceptible animals, it is difficult to conceive of the infection in man failing to yield similarly to the administration of such sera.


2019 ◽  
pp. 168-176
Author(s):  
I. N. Zakharova ◽  
A. N. Kas’yanova

Human skin is the largest yet complex organ that performs many functions. The skin barrier is crucial for survival, preventing moisture loss and the entry of infectious or toxic substances. Skin is also a complex habitat for a diverse population of microbiota. During childbirth and subsequent exposure to the postnatal environment, the skin is colonized by many microbes, many of which are commensal or symbiotic. The useful functions of the resident microbiota include inhibition of pathogenic species through various mechanisms that are actively studied. Modern research is increasingly focused on the role of human microbiomes, including skin microbioms, in the development of a range of pathological diseases, including dermatological, allergic and infectious diseases. Due to the growing spread of the 16S rRNA bacteria gene sequencing method, more and more information on the microbial composition of various body systems, including the skin, is becoming available every year. The review presents current data on the composition of a healthy skin microbiome and its changes over the course of human’s life, and demonstrates some mechanisms of its effect on the health of the skin and the body as a whole. Special attention is paid to the concept of ecological niches of skin, their peculiarities and unique microbial composition. The role of microbiomal abnormalities in the development of a number of chronic inflammatory skin diseases, including atopic dermatitis, psoriasis and acne, was also analyzed.


Author(s):  
G. S. Agzamova ◽  
M. M. Abdullaeva

The immunological profile of chronic liver lesions depending on the toxic agent was studied. It was revealed that chronic poisoning by industrial toxic substances causes changes in the functional state of the T-system of immunity, long-term contact with industrial chemicals leads to increased sensitization to autoantigens of the body.


2020 ◽  
pp. 45-52
Author(s):  
S. Schetinin

The analysis of the clinical and immunological effectiveness of ozone therapy is carried out. The mechanism of the bactericidal action of ozone in the treatment of infectious and inflammatory diseases of a bacterial and viral nature is analyzed. Ozonation of oils leads to the formation of a complex and heterogeneous cascade of components. Ozonides provide the body with some prolonged supply of active oxygen to maintain aerobic metabolism and the required level of energy substrates.


2018 ◽  
Vol 24 (14) ◽  
pp. 1533-1550 ◽  
Author(s):  
Jong-Eun Kim ◽  
Ki Won Lee

Skin is a protective organ and the largest of the human body. Due to its pivotal role in aesthetic appearance, skin health has a significant impact on quality of life. Chronic inflammation of the skin often marks the beginning of various skin diseases. Immune-mediated responses serve to protect the body from external insults and require succinct control, and can lead to ongoing cellular damage and various skin conditions if left unchecked. Studies have shown that phytochemicals can alter processes involved in skin inflammation and alleviate the effects of aging, cancer, atopic dermatitis, psoriasis, and vitiligo. Direct molecular targets of some phytochemicals have been identified and their precise mechanisms of action investigated. In this review, we summarize recent findings on the effects of phytochemicals on skin inflammation and the mechanisms of action involved.


2020 ◽  
Vol 26 (44) ◽  
pp. 5720-5731 ◽  
Author(s):  
Arun Singh Lalotra ◽  
Vishesh Singh ◽  
Bharat Khurana ◽  
Shelly Agrawal ◽  
Shubham Shrestha ◽  
...  

Background: Skin is the largest organ of the body and helps to regulate several physiological functions. It acts as a barrier that protects the body against UV-radiation, toxic substances, infections, etc. The abnormal growth of the skin cells is called skin cancer. Different types of skin cancer can be classified as Basal Cell Carcinoma (BCC) and Squamous Cell Carcinoma (SCC); which mainly occur due to chronic exposure to UV- sunlight and pollution. Methods: The conventional topical treatments of skin cancer such as cream, gel, ointment, etc., are more occlusive and thus they do not penetrate deep into the skin (dermal layer) and remain at the upper part of the skin (epidermal layer). The stratum corneum acts as a physiological barrier for the drug-loaded in the conventional formulation. The novel carrier systems have the potential to facilitate the penetration of the drug deep into the skin (dermal layer) because these have less size and higher flexibility than conventional treatment. Conclusion: In the present review, we have discussed various novel carrier systems being investigated for the topical application of chemotherapeutic agents for efficient skin targeting and better dermatological as well as therapeutic benefits with minimal systemic exposure and toxicity.


2019 ◽  
Vol 19 (10) ◽  
pp. 826-832 ◽  
Author(s):  
Zhi-Gang Sun ◽  
Ting-Ting Zhao ◽  
Na Lu ◽  
Yong-An Yang ◽  
Hai-Liang Zhu

Glycyrrhizic acid (GA), a triterpene isolated from the roots and rhizomes of licorice, named Glycyrrhiza glabra, is the principal bioactive ingredient of anti-viral, anti-inflammatory and hepatoprotective effects. GA has been used in the clinical treatment of hepatitis, bronchitis, gastric ulcer, AIDS (acquired immunodeficiency syndrome), certain cancers and skin diseases. It has a direct effect on anti-HBV (hepatitis B virus) via affecting the HBsAg (hepatitis B surface antigen) to extracellular secretion, improving liver dysfunction in patients with chronic hepatitis B, and ultimately improving the immune status of HBV. GA can significantly inhibit the proliferation of HIV, showing an immune activation. The clinical application of GA on the prevention and treatments of various diseases may derive from its numerous pharmacological properties. This review provides the summary of the antiviral effects of GA on research progress and mechanism in recent years.


Author(s):  
Wang Gong ◽  
Fei Wang ◽  
Yuqing He ◽  
Blake Heath ◽  
Xin Zeng ◽  
...  

: Mesenchymal stem cell (MSC) therapy for clinical diseases associated with inflammation and tissue damage has become a progressive treatment strategy. MSCs have unique biological functions, such as homing, immune regulation, and differentiation capabilities, which provide the prerequisites for treatment of clinical diseases. Oral diseases are often associated with abnormal immune regulation and epithelial tissue damage. In this review, we summarize previous studies that use MSC therapy to treat various oral inflammatory diseases, including oral ulceration, allergic diseases, chemo/radiotherapy-induced oral mucositis, periodontitis, osteonecrosis of the jaw, Sjögren's syndrome (SS), among other similar diseases. We highlight MSC treatment as a promising approach in the management of oral inflammatory diseases, and discuss the obstacles that remain and must be overcome for MSC treatment to thrive in the future.


2020 ◽  
Vol 15 (7) ◽  
pp. 559-569 ◽  
Author(s):  
Zhen Chang ◽  
Youhan Wang ◽  
Chang Liu ◽  
Wanli Smith ◽  
Lingbo Kong

Macrophages M2 polarization have been taken as an anti-inflammatory progression during inflammation. Natural plant-derived products, with potential therapeutic and preventive activities against inflammatory diseases, have received increasing attention in recent years because of their whole regulative effects and specific pharmacological activities. However, the molecular mechanisms about how different kinds of natural compounds regulate macrophages polarization still unclear. Therefore, in the current review, we summarized the detailed research progress on the active compounds derived from herbal plants with regulating effects on macrophages, especially M2 polarization. These natural occurring compounds including flavonoids, terpenoids, glycosides, lignans, coumarins, alkaloids, polyphenols and quinones. In addition, we extensively discussed the cellular mechanisms underlying the M2 polarization for each compound, which could provide potential therapeutic strategies aiming macrophages M2 polarization.


Author(s):  
Robert Laumbach ◽  
Michael Gochfeld

This chapter describes the basic principles of toxicology and their application to occupational and environmental health. Topics covered include pathways that toxic substances may take from sources in the environment to molecular targets in the cells of the body where toxic effects occur. These pathways include routes of exposure, absorption into the body, distribution to organs and tissues, metabolism, storage, and excretion. The various types of toxicological endpoints are discussed, along with the concepts of dose-response relationships, threshold doses, and the basis of interindividual differences and interspecies differences in response to exposure to toxic substances. The diversity of cellular and molecular mechanisms of toxicity, including enzyme induction and inhibition, oxidative stress, mutagenesis, carcinogenesis, and teratogenesis, are discussed and the chapter concludes with examples of practical applications in clinical evaluation and in toxicity testing.


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